啮齿类动物致癌性试验的关注要点  

Points to consider for rodent carcinogenicity studies

作　　者：张云 李定洲 黄芳华 孙涛 SELLERS Rani KHAN Nasir ZHANG Yun;LI Ding-zhou;HUANG Fang-hua;SUN Tao;SELLERS Rani;KHAN Nasir(Drug Safety Research&Development,Pfizer,New York 10965,USA;Drug Safety Research&Development,Pfizer,Connecticut 06340,USA;Center of Drug Evaluation,National Medical Product Administration,Beijing 100022,China)

机构地区：[1]辉瑞制药公司全球研究开发药物安全研究与发展部,美国纽约10965 [2]辉瑞制药公司全球药物安全研究与发展部,美国康涅狄格州06340 [3]国家药品监督管理局药品审评中心,北京100022

出　　处：《中国临床药理学杂志》2022年第10期1151-1160,共10页The Chinese Journal of Clinical Pharmacology

摘　　要：啮齿类动物致癌性试验的目的是确定候选药物在动物中是否具有致癌性,以及如果存在致癌性风险,这种风险是否会转化至人类。药物相关的致癌作用可能表现为肿瘤发生率增加、背景肿瘤发生潜伏期缩短或罕见肿瘤的发生。本文重点讨论啮齿类动物致癌性试验中的一些具体而关键的内容,包括试验设计、实施、报告和结果解释分析的考虑要点。本文重点阐述致癌性试验进行的时间、试验设计的关键方面(剂量选择、种属选择、如何处理早期死亡和试验组终止等)、试验报告的一般内容和注意事项、致癌性试验数据的统计分析和结果阐述分析等。使用综合证据权重(WoE)方法解释致癌性试验结果,尤其对啮齿类动物致癌试验发现是否与人体致癌风险相关的评价是至关重要的。The goal of rodent carcinogenicity studies is to determine whether a drug candidate has carcinogenic potential in animal models and,if it does,how this risk translates to humans.Drug-related carcinogenicity effects may present as increased tumor incidence,shortened latency to onset of background tumors,or the development of rare neoplasms.This article focused on some practical and key considerations in rodent carcinogenicity studies,and the purpose of this article was to provide points to consider for the study design,execution,report,and data interpretation.These included timing of study conduct,key aspects of study design(e.g.,dose selection,species/strain selection,managing early mortality and study group terminations),and study report format/content and general considerations,using statistics to understand carcinogenic risk,and what to consider when determining human risk,etc.The use of an integrative weight-of-evidence(WoE)approach to interpret study findings is essential to translating rodent carcinogenicity potential to human carcinogenicity risk.

关 键 词：非临床安全性评价 啮齿类动物致癌性试验 人类相关性 证据权重 

分 类 号：R97[医药卫生—药品]